Molecular dispensers

ABSTRACT

A method for dispensing charged particles includes applying a bias voltage to promote motion of charged molecules through a nanopore, detecting passage of at least one charged molecule through the nanopore, and manipulating an electrostatic potential barrier inside the nanopore, so as to prevent movement of additional charged molecules through the nanopore.

CROSS-REFERENCE TO RELATED APPLICATION

This application is a continuation of U.S. patent application Ser. No.13/162,833, filed Jun. 17, 2011, the disclosure of which is incorporatedby reference herein in its entirety.

BACKGROUND

The present invention relates generally to nanotechnology, and morespecifically, example embodiments of the present invention are directedto nano-scaled apertures configured to accurately transmit individualcharged entities, for example, molecules or particles such as beads.

Generally, nano-scaled apertures may be considered nanopores, orapertures on the scale of 1-100 nanometers of internal diameter.Semiconductor nanopores may be produced through a variety of methods,including the formation of an aperture several nanometers to severaltens or hundreds of nanometers of internal diameter through asemiconductor substrate. Depending on the desired pore diameter, avariety of techniques may be used to create the pore. For example,electron beam drilling with a transmission electron microscope, reactiveion etching, or ion-beam sculpting may be used to create a pore ofspecified diameter. The final aperture may be on the scale of 1-100nanometers, and may be considered a nanopore.

SUMMARY

According to one embodiment of the present invention, a method fordispensing charged particles includes applying a bias voltage to promotemotion of charged molecules through a nanopore, detecting passage of atleast one charged molecule through the nanopore, and manipulating anelectrostatic potential barrier inside the nanopore, so as to preventmovement of additional charged molecules through the nanopore.

According to another embodiment of the present invention, a moleculardispenser includes a molecular reservoir comprising a plurality ofcharged molecules, a nanopore proximate the molecular reservoir, a firstdrag electrode arranged within the molecular reservoir, and a controlunit. The nanopore comprises a first set of locking electrodesconfigured to establish an electrostatic potential barrier therein.According to the example embodiment, the control unit is configured toapply an oscillating voltage across the first set of locking electrodesand a bias voltage to the first drag electrode to control flow ofindividually charged molecules from the molecular reservoir through thenanopore

Additional features and advantages are realized through the techniquesof the present invention. Other embodiments and aspects of the inventionare described in detail herein and are considered a part of the claimedinvention. For a better understanding of the invention with theadvantages and the features, refer to the description and to thedrawings.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

The subject matter which is regarded as the invention is particularlypointed out and distinctly claimed in the claims at the conclusion ofthe specification. The forgoing and other features, and advantages ofthe invention are apparent from the following detailed description takenin conjunction with the accompanying drawings in which:

FIG. 1 depicts a schematic cross sectional view of a moleculardispenser, according to an example embodiment;

FIG. 2 depicts a schematic cross sectional view of a moleculardispenser, according to an example embodiment;

FIG. 3 depicts a graph of time-dependent ratcheting voltages of amolecular dispenser, according to an example embodiment;

FIG. 4 depicts a perspective view of molecular dispenser sieve,according to an example embodiment;

FIG. 5 is a flow diagram illustrating a method of dispensing molecules,according to an example embodiment; and

FIG. 6 is a flow diagram illustrating a method of dispensing molecules,according to an example embodiment.

DETAILED DESCRIPTION

Precisely controlling the concentration of a chemical compound (e.g.,protein) in a solution is a challenge. Example embodiments providemolecular dispensers which greatly increase the accuracy of control ofdispensation through a nanopore structure comprising at least onenanopore. The technical effects and benefits of the nanopore structureinclude an ability to dispense a precisely controlled count ofindividual molecules into a desired solution. As used herein, a nanoporerefers to a nano-scaled aperture or through-hole entirely penetrating amaterial, for example, a membrane.

FIG. 1 is a diagram illustrating a cross-section of a moleculardispenser device, according to an embodiment of the present invention.The device 100 includes a control unit 109 and a nanopore membrane 102in communication with the control unit. The nanopore membrane 102 may becoated with an electrical insulator such as silicon oxide on both sidesof the membrane. The nanopore membrane 102 defines at least one nanopore105 extending therethrough.

The nanopore membrane 102 includes at least one electrode 106 arrangedtherein in communication with the control unit 109 via medium 120 (e.g.,channel or wire), the at least one electrode 106 further defining thenanopore 105 extending therethrough. For example, the electrode 106 maybe substantially planar having a substantially circular hole whichdefines the nanopore 105. Thus, the interior dimensions of nanopore 105may be substantially cylindrical, with electrode 106 surrounding thenanopore (e.g., see FIG. 4).

According to the illustrated embodiment, the nanopore membrane 102 mayfurther include an insulating layer 115 proximate the electrode 106, asecond electrode 107 proximate the insulating layer 115 and incommunication with the control unit 109 via medium 121, a secondinsulating layer 116 proximate the second electrode 107, and may includea third electrode 108 proximate the second insulating layer 116 and incommunication with the control unit 109 via medium 122. The insulatinglayers may be formed of any suitable insulator, including silicondioxide, for example. The electrodes may be formed of any suitableelectrically conducting material or metal.

By way of illustration, FIG. 1 depicts an arrangement of the device 100for transferring a charged entity or charged molecule 113 from amolecular reservoir portion 103 (preceding the nanopore) to a targetsolution portion 104 (following the nanopore). The membrane 102 isformed as a stack of the electrodes 106, 107, 108 separated by theinsulating layers 115 and 116. The electrical potential of eachelectrode (V₁, V₂, and V₃) is set independently by control unit 109.Electrodes 106 and 107 are referred to as locking electrodes herein.Electrode 108 is referred to as a counter or detector electrode herein.V₁, V₂, V₃ are the respective voltages for electrodes 106, 107, 108.

Portion 103 and portion 104 are connected by a nanopore 105 in thenanopore membrane 102. Locking electrodes (for example, 106 and 107) arecapable of creating an electrostatic potential barrier 114 inside thenanopore 105 by, for example, creating a potential difference betweenthe electrodes to impede flow through the nanopore 105.

Control unit 109 provides bias voltage (V_(c)) to electrode 110 inportion 103 via electrical communication medium 123, and also providesbias voltage (V_(t)) to electrode 111 in portion 104 via electricalcommunication medium 124. Electrodes 110 and 111 are referred to as dragelectrodes. The drag electrodes may be formed of any suitableelectrically conducting material or metal, including silver. The dragelectrodes may be fixed in space within respective portions 103 and 104,or may be positioned relatively proximate an entry and exit of thenanopore 105. The drag electrodes may be biased to compel movement ofthe charged molecules 113 through the nanopore 105.

Charged molecules 113 may be, for example, originally located inmolecular reservoir portion 103. The voltage difference V_(t)−V_(c)(drag voltage) attracts the charged molecules towards portion 104.Control unit 109 detects the passage of a charged molecule inside thenanopore 105. The detection can be accomplished, for example, bymeasuring the variation of ion current between drag electrodes 110 and111, locking electrodes 106 and 107, and/or counter electrode 108.According to an example embodiment, passage detection is facilitated bydetection of a variation of voltage or current at the counter electrode108. According to other example embodiments, passage detection isfacilitated by measurement between drag electrode 110 and drag electrode111 singularly or in combination with measurement from counter electrode108. It is to be appreciated, however, that measurements can also madeusing any combination of locking, counter, and drag electrodes.

Upon or prior to passage of a molecule within the nanopore 105, lockingvoltages are applied to locking electrodes (for example, 106, 107) tocreate the potential barrier 114. The potential barrier 114 may beoscillated in a ratcheting manner to compel sequential passage ofindividual charged molecules through the nanopore 105 by application oftime-dependent voltage biases to the locking electrodes 106 and 107.Upon passage of a desired number of charged molecules, the bias voltagesof the drag electrodes 110 and 111 may be removed. The drag electrodesand locking electrodes can be controlled independently, or can becontrolled in parallel, for example, through use of simple logic gateswith the application of at least one oscillating control signal.

As illustrated, three electrodes are used within the electrode stack ofthe membrane 102. It is to be appreciated, however, that one or morelocking electrodes may be used in other embodiments. In an embodimentwhere a single locking electrode is used, a potential barrier is createdas a result of the voltage of the locking electrode. For example, alocking electrode with a voltage of 0.4 Volt may create a potentialbarrier in a surrounding environment of neutral voltage or a dragvoltage of 0.8 Volt. Furthermore, a plurality of potential barriers maybe produces through use of multiple electrodes stacked through thelength of a nanopore.

In FIG. 1, locking electrodes 106, 107 and 108 are shown to havecylindrical geometry (for example, metal plane with a holetherethrough). In other embodiments of the present invention, however,the geometry of the locking electrodes and drag electrodes can vary. Byway of example, an example embodiment may include two electrodes perlayer, each occupying a portion of a half plane with a hole in thecenter.

As illustrated, example embodiments may include the control unit 109. Itis to be appreciated, however, that other embodiments may include one ormore control units. A control unit may include, for example, a computerthat connects to a specialized board with an application-specificintegrated circuit (ASIC), wherein the board connects to the device. Acontrol unit may also, for example, be integrated with the device by wayof a Nano-Electro-Mechanical System (NEMS), wherein a nanofluidicsportion (for example, a reservoir of charged molecules) can be combinedwith electronics (for example, a control unit). The control unit appliesbias voltages to the drag electrodes to attract a charged molecule froma molecular reservoir portion of a reservoir to a target solutionportion of a reservoir, as well as applying a time-dependent oroscillating voltage to each locking electrode to create an electrostaticpotential barrier, wherein the electrostatic potential barrier controlsthe passage of individual charged molecules through a nanopore.

Moreover, in an example embodiment of the present invention, the controlunit implements detection of entry of the charged molecule inside thenanopore, and altering the time-dependent voltages from the lockingelectrodes.

Also, in one or more embodiments of the present invention, the controlunit may implement repetition of one or more actions. Such actions mayinclude, for example, reducing or removing the bias voltages from thedrag electrodes, and increasing or re-applying the time-dependentvoltage to each locking electrode to create and manipulate anelectrostatic potential barrier in a ratcheting manner. Such repeatedactions may also include, for example, performing one or morecharacterization activities of a target solution including individualmolecule counting and resolution, reducing or removing thetime-dependent voltage from each locking electrode and the electrostaticpotential barrier, and increasing or re-applying the bias voltages tothe drag electrodes to transfer the charged molecules from the molecularreservoir 103 to the target solution 104.

In an illustrative embodiment of the invention, the control unitimplements repetition of the above steps until a desired or targetcomposition of a target solution is reached.

Although illustrated and described above as including a single potentialbarrier, it should be appreciated that the same may be varied to furtherincrease the molecular dispensing accuracy of example embodiments. Forexample, FIG. 2 is a diagram illustrating a cross-section of a moleculardispenser device implementing a plurality of potential barriers,according to an embodiment of the present invention.

The device 200 includes a control unit 209 and a nanopore membrane 202in communication with the control unit. The nanopore membrane 202defines at least one nanopore 205 extending therethrough. The nanoporemembrane 202 includes electrodes 206, 207, 208, 241, 242, and 243arranged therein in communication with the control unit 209 via mediums220, 221, 222, 230, 231, and 232 (e.g., channels or wires). Eachelectrode further defines the nanopore 205 extending therethrough. Forexample, the electrodes may be substantially planar having asubstantially circular hole which defines the nanopore 205. Thus, theinterior dimensions of nanopore 205 may be substantially cylindrical,with electrodes surrounding the nanopore (e.g., see FIG. 4).

According to the illustrated embodiment, the nanopore membrane 202 mayfurther include insulating layers 215, 216, 217, 218, and 219 arrangedbetween adjacent electrodes forming an electrode stack somewhatsimilarly as in FIG. 1. The insulating layers may be formed of anysuitable insulator, including silicon dioxide, for example. Theelectrodes may be formed of any suitable electrically conductingmaterial or metal.

By way of illustration, FIG. 2 depicts an arrangement of the device 200for transferring a charged molecule 213 from a molecular reservoirportion 203 (preceding the nanopore) to a target solution portion 204(following the nanopore) more accurately as compared to the device 100.The electrical potential of each electrode (V₁, V₂, V₃, V₄, V₅, and V₆)is set independently by control unit 209. Electrodes 206, 207, 241, and242 are referred to as locking electrodes herein. Electrodes 208 and 243referred to as counter or detector electrodes herein. Furthermore,electrodes 206, 207, and 208 may be grouped and referred to as a firstset of ratcheting/locking electrodes 251, while electrodes 241, 242, and243 may be grouped and referred to as a second set of ratcheting/lockingelectrodes 252.

Portion 203 and portion 204 are connected by the nanopore 205 in thenanopore membrane 202. Locking electrodes (for example, 206, 207, 241,and 242) are capable of creating electrostatic potential barriers 214and 244 inside the nanopore 205 by, for example, creating a potentialdifference between the electrodes to impede flow through the nanopore205.

Control unit 209 provides bias voltage (V_(c)) to electrode 210 inportion 203 via electrical communication medium 223, and also providesbias voltage (V_(t)) to electrode 211 in portion 204 via electricalcommunication medium 224. Electrodes 210 and 211 are referred to as dragelectrodes. The drag electrodes may be formed of any suitableelectrically conducting material or metal, including silver. The dragelectrodes may be fixed in space within respective portions 203 and 204,or may be positioned relatively proximate an entry and exit of thenanopore 205. The drag electrodes may be biased to compel movement ofthe charged molecules 213 through the nanopore 205.

Charged molecules 213 may be, for example, originally located inmolecular reservoir portion 203. The voltage difference V_(t)−V_(c)(drag voltage) attracts the charged molecules towards portion 204.Control unit 209 detects the passage of a charged molecule inside thenanopore 205. The detection can be accomplished, for example, bymeasuring the variation of ion current between drag electrodes 210 and211, locking electrodes 206, 207, 241, 242, and/or counter electrodes208 and 243. According to an example embodiment, passage detection isfacilitated by the counter electrodes 208 and 243. According to otherexample embodiments, passage detection is facilitated by measurementbetween drag electrode 210 and drag electrode 211 singularly or incombination with measurement from counter electrodes 208 and 241. It isto be appreciated, however, that measurements can also made using anycombination of locking, counter, and drag electrodes.

Upon or prior to passage of a molecule within the nanopore 205, lockingvoltages are applied to locking electrodes to create the potentialbarrier 214. The potential barrier 214 may be oscillated in a ratchetingmanner to compel sequential passage of individual charged moleculesthrough the nanopore 205 by application of time-dependent voltage biasesto first set of ratcheting/locking electrodes 251. Upon passage of asingle charged molecule past the counter electrode 208, time-dependentvoltage biases may be applied to the second set of ratcheting/lockingelectrodes 252, while a locking voltage is applied to the lockingelectrodes 206 and 207. In this manner, a single charged molecule may bepassed through a dual-ratchet arrangement of potential barriers, therebyincreasing the effectiveness of the device 200 as compared to the device100 with regards to passage of single molecules through a nanopore.

Upon passage of a desired or target number of molecules through thenanopore 205, the bias voltages of the drag electrodes 210 and 211 maybe removed. The drag electrodes and locking electrodes (e.g., individualsets of ratcheting electrodes) can be controlled independently, or canbe controlled in parallel, for example, through use of simple logicgates with the application of at least one oscillating control signal.According to an example embodiment of the present invention, at leasttwo oscillating signals are applied, a first oscillating signal beingapplied to the first set of ratcheting/locking electrodes 251, and asecond oscillating signal being applied to the second set ofratcheting/locking electrodes 252. According to this embodiment, thefrequencies of the first and second oscillating signals may bedifferent, with one operating at a higher frequency.

In order to better understand the creation of a potential barrier foroscillation in a ratcheting manner, FIG. 3 is provided. FIG. 3 is adiagram illustrating example applications of time-dependent voltages,according to an embodiment of the present invention. By way ofillustration, FIG. 3 depicts three positions, a lock position 310, amove position 311, and a lock position 312, of the device arrangementillustrated in FIG. 1. It should be appreciated that the same voltagebias information is easily extensible to the dual-ratchet arrangement ofFIG. 2. As shown, the bias voltage 301 of electrode 106 oscillates froma positive value to a lower value and the bias voltage 302 of theelectrode 107 oscillates from a neutral value to a positive value inorder to disable the potential barrier 114. Further, steady applicationof a bias voltage to the electrodes 110 and 111 (e.g., voltages 303-304)results in a steady electrostatic force compelling motion of the chargedparticles towards and through a nanopore, being impeded only byoscillation of the voltages 301 and 302 to a lock position.

It should be readily appreciated that while described singularly,nanopores are useable in combination, such as, for example, in anano-sieve as illustrated in FIG. 4. As shown, the sieve 400 includes ananopore membrane 402 comprising a plurality of nanopores 105, eachunder the control of an independent or combined control unit.Alternatively, the nanopore membrane may also include additionalnanopores of different design, for example, including nanopores 205. Asdepicted, the sieve 400 provides a barrier between reservoirs 403 and404, such that very precise control over passage of charges molecules113 is possible.

It should be readily appreciated that sieve 400 may comprise a pluralityof nanopores of different sizes (e.g., diameters, depths, etc) for theseparation and organization of molecules by size and charge.

It should further be appreciated that sieve 400 may enable the precisedetermination of molecular density or quantity of a solution throughcounting of molecules passing through respective nanopores of the sieve400.

It should further be appreciated that sieve 400 may be scaled tomillions of nanopores operating simultaneously and independently toprovide a faster result.

It should further be appreciated that a plurality of sieves 400 may beused in a system for dispensing molecules. Each sieve of the pluralityof sieves may be configured to transport molecules of a different typeto a single target solution, thereby facilitating formation of complexbut accurate mixtures of molecules.

It should further be appreciated although particularly described astransferring charged molecules only, polymer capsules with a netelectrical charge may be used to facilitate transfer ofelectrically-neutral payloads.

As described above, molecular dispensers are provided whichsignificantly increase the accuracy of creating or measuring solutionsthrough the restricted passage of molecular compounds through one ormore nanopores. Each nanopore may include at least one electrodeconfigured to provide an electrostatic potential barrier to passage ofmolecules therethrough. Furthermore, adjacent reservoirs, a molecularreservoir comprising suspended molecules and a target solution reservoirfor creation of a target solution, may be electrically biased such thatmolecules from the molecular reservoir are compelled to motion towardsand through the one or more nanopores. Moreover, ratcheting applicationof a time-dependent voltage on the at least one electrode provides aratcheting action to transport molecules in a singular, sequentialmanner from the molecular reservoir to the target solution reservoir.

Hereinafter, a more detailed description of methodologies of moleculardispensing are described with references to FIGS. 5-6.

Turning to FIG. 5, the method 500 includes applying a drag voltageacross drag electrodes of a molecular dispenser at block 501. The dragvoltage may be any amount of voltage suitable for compelling motion ofsuspended molecules through a nanopore. The molecular dispenser may beany suitable dispenser comprising a control unit and at least onenanopore arranged to transfer molecules. The drag electrodes may besuspended in adjacent solution reservoirs, for example, a molecularreservoir and a target solution reservoir, and may be biased by thecontrol unit.

The method 500 further includes applying a locking voltage acrosslocking electrodes of the molecular dispenser at block 502. The lockingvoltage may be a voltage bias greater than or equal to a surroundingelectrostatic potential, for example, such that application of thelocking voltage forms an electrostatic potential barrier proximate thelocking electrodes and within the nanopore, which blocks transfer ofmolecules therethrough (e.g., see. FIG. 3.)

The method 500 further includes determining if more molecules are neededin the target solution reservoir at block 503. If more molecules areneeded, the method 500 includes applying a move/ratcheting voltageacross the locking electrodes at block 505. The ratcheting voltage maybe a voltage bias sufficient to allow travel of a molecule, or a voltagebias configured to push a molecule through a portion of the nanopore.The method 500 further includes detecting passage of a molecule throughthe at least one nanopore at block 506. For example, detection may befacilitated through the control unit by detecting voltage variationsacross the drag electrodes and/or through use of a counter electrodearranged around the nanopore. Thereafter, the method returns to block502 for additional ratcheting as described above.

If more molecules are not needed as determined at block 503, the targetsolution may be extracted or otherwise used at block 504. It should beappreciated that this method of molecular dispensing is also reversible,for removal of molecules from the target solution reservoir, throughapplication of reverse voltage bias. Moreover, it should also beunderstood that block 503 is easily replaceable with any suitabledecision, for example, if using the molecular dispenser as an analysistool to count available molecules from the molecular reservoir.

As described above, molecular dispensers are not limited to dispensersincluding nanopores with a single set of ratcheting/locking electrodes.For example, according to some example embodiments (e.g., FIG. 2),nanopores may include two or more sets of ratcheting/locking electrodes.

Turning to FIG. 6, a method of dispensing molecules is illustrated. Themethod 600 includes applying a drag voltage across drag electrodes of amolecular dispenser at block 601. The drag voltage may be any amount ofvoltage suitable for compelling motion of suspended molecules through ananopore. The molecular dispenser may be any suitable dispensercomprising a control unit and at least one nanopore arranged to transfermolecules (e.g., dispenser 200). The drag electrodes may be suspended inadjacent solution reservoirs, for example, a molecular reservoir and atarget solution reservoir, and may be biased by the control unit.

The method 600 further includes operating a first set of lockingelectrodes at a first frequency at block 602 (e.g., at a firstoscillating voltage), and operating a second set of locking electrodesat a second frequency at block 603 (e.g., at a second oscillatingvoltage). Operating the first set of locking electrodes includesperforming method steps 502-506 for the first set of locking electrodesat the first frequency. For example, by oscillating from a first lockingvoltage and first ratcheting voltage at the first frequency. Similarly,operating the second set of electrodes at the second frequency includesperforming method steps 502-506 for the second set of locking electrodesat the second frequency. For example, by oscillating from a secondlocking voltage and second ratcheting voltage at the second frequency.According to one example embodiment, the first frequency and the secondfrequency are the same frequency. According to another exampleembodiment, the first frequency and the second frequency are different.According to another example embodiment, the first frequency is lowerthan the second frequency. According to another example embodiment, thefirst frequency and the second frequency are out of phase, such that thefirst set of locking electrodes are locked if the second set of lockingelectrodes are open (e.g., no potential barrier applied), and viceversa.

Turning back to FIG. 6, the method 600 further includes determining ifmore molecules are needed in the target solution reservoir at block 604.If more molecules are not needed, the target solution may be extractedor otherwise utilized at block 605.

It is noted that the terminology used herein is for the purpose ofdescribing particular embodiments only and is not intended to belimiting of the invention. As used herein, the singular forms “a”, “an”and “the” are intended to include the plural forms as well, unless thecontext clearly indicates otherwise. It will be further understood thatthe terms “comprises” and/or “comprising,” when used in thisspecification, specify the presence of stated features, integers, steps,operations, elements, and/or components, but do not preclude thepresence or addition of one more other features, integers, steps,operations, element components, and/or groups thereof.

The corresponding structures, materials, acts, and equivalents of allmeans or step plus function elements in the claims below are intended toinclude any structure, material, or act for performing the function incombination with other claimed elements as specifically claimed. Thedescription of the present invention has been presented for purposes ofillustration and description, but is not intended to be exhaustive orlimited to the invention in the form disclosed. Many modifications andvariations will be apparent to those of ordinary skill in the artwithout departing from the scope and spirit of the invention. Theembodiment was chosen and described in order to best explain theprinciples of the invention and the practical application, and to enableothers of ordinary skill in the art to understand the invention forvarious embodiments with various modifications as are suited to theparticular use contemplated.

The flow diagrams depicted herein are just one example. There may bemany variations to this diagram or the steps (or operations) describedtherein without departing from the spirit of the invention. Forinstance, the steps may be performed in a differing order or steps maybe added, deleted or modified. All of these variations are considered apart of the claimed invention.

While particular embodiments of the invention have been described, itwill be understood that those skilled in the art, both now and in thefuture, may make various improvements and enhancements which fall withinthe scope of the claims which follow. These claims should be construedto maintain the proper protection for the invention first described.

1. A molecular dispenser, comprising: a molecular reservoir comprising aplurality of charged molecules; a nanopore proximate the molecularreservoir, the nanopore comprising a first set of locking electrodesconfigured to establish an electrostatic potential barrier therein; afirst drag electrode arranged within the molecular reservoir; and acontrol unit, wherein the control unit is configured to apply anoscillating voltage across the first set of locking electrodes and abias voltage to the first drag electrode to control flow of individuallycharged molecules from the molecular reservoir through the nanopore. 2.The molecular dispenser of claim 1, wherein the nanopore furthercomprises a second set of locking electrodes configured to establish asecond electrostatic potential barrier therein.
 3. The moleculardispenser of claim 2, there control unit is further configured to applya second oscillating voltage across the second set of locking electrodesto control flow of individually charged molecules from the molecularreservoir through the nanopore.
 4. The molecular dispenser of claim 2,wherein the first set of locking electrodes and the second set oflocking electrodes each comprise: a first electrode; an insulating layerproximate the first electrode; and a second electrode proximate theinsulating layer.
 5. The molecular dispenser of claim 4, wherein thefirst electrode, the insulating layer, and the second electrode of boththe first set of locking electrodes and the second set of lockingelectrodes are substantially planar and stacked to form a nanoporemembrane.
 6. The molecular dispenser of claim 4, wherein the first setof locking electrodes and the second set of locking electrodes eachfurther comprise: a second insulating layer proximate the secondelectrode; and a counter electrode proximate the second insulatinglayer, wherein the counter electrode is configured to detect passage ofcharged molecules through the nanopore.
 7. The molecular dispenser ofclaim 1, wherein the nanopore further comprises a counter electrodeconfigured to detect passage of charged molecules through the nanopore.8. The molecular dispenser of claim 1, wherein the first set of lockingelectrodes comprise: a first electrode; an insulating layer proximatethe first electrode; and a second electrode proximate the insulatinglayer.
 9. The molecular dispenser of claim 5, wherein the firstelectrode, the insulating layer, and the second electrode aresubstantially planar and stacked to form a nanopore membrane.
 10. Themolecular dispenser of claim 1, further comprising a target solutionreservoir proximate the nanopore, the target solution reservoirconfigured to receive charged molecules transferred through thenanopore.